Role of Sam68 as an adaptor protein in signal transduction

Najib, Souad; Martín-Romero, Consuelo; González-Yanes, Carmen; Sánchez-Margalet, Vı́ctor

doi:10.1007/s00018-004-4309-3

Cited by 57 publications

(62 citation statements)

References 93 publications

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“…Elevated expression of IGF-II is often observed in human gastric cancer tissues, especially in the infiltrative-type cancers (29), and the paracrine or autocrine pathway of IGF-II causes a significant increase in the PI3-kinase and Akt pathway, which rescues cells from apoptosis (5). It was reported previously that cross talk occurs between SFKs and a factor that mediates nucleic acid-directed processes, a Src-associated substrate during mitosis, the 68-kDa protein Sam68, which belongs to the family of KH domain-containing RNA-binding proteins, and that its tyrosine phosphorylation via interaction with SFKs causes a decreased affinity for RNA (20,21). On the other hand, the RNA-binding capacity of Ossa was not altered by phosphorylation via SFKs (Fig.…”

Section: Discussionmentioning

confidence: 78%

A Novel RNA-Binding Protein, Ossa/C9orf10, Regulates Activity of Src Kinases To Protect Cells from Oxidative Stress-Induced Apoptosis

Tanaka¹,

Sasaki

Kamata³

et al. 2009

Molecular and Cellular Biology

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During the process of tumor progression and clinical treatments, tumor cells are exposed to oxidative stress. Tumor cells are frequently resistant to such stress by producing antiapoptotic signaling, including activation of Src family kinases (SFKs), although the molecular mechanism is not clear. In an attempt to identify the SFK-binding proteins selectively phosphorylated in gastric scirrhous carcinoma, we identified an uncharacterized protein, C9orf10. Here we report that C9orf10 (designated Ossa for oxidative stressassociated Src activator) is a novel RNA-binding protein that guards cancer cells from oxidative stressinduced apoptosis by activation of SFKs. Exposure to oxidative stress such as UV irradiation induces the association of Ossa/C9orf10 with regulatory domains of SFKs, which activates these kinases and causes marked tyrosine phosphorylation of C9orf10 in turn. Tyrosine-phosphorylated Ossa recruits p85 subunits of phosphatidylinositol 3-kinase (PI3-kinase) and behaves as a scaffolding protein for PI3-kinase and SFKs, which activates the Akt-mediated antiapoptotic pathway. On the other hand, the carboxyl terminus of Ossa has a distinct function that directly binds RNAs such as insulin-like growth factor II (IGF-II) mRNA and promotes the extracellular secretion of IGF-II. Our findings indicate that Ossa is a dualfunctional protein and might be a novel therapeutic target which modulates the sensitivity of tumors to oxidative stress.

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Section: Discussionmentioning

confidence: 78%

A Novel RNA-Binding Protein, Ossa/C9orf10, Regulates Activity of Src Kinases To Protect Cells from Oxidative Stress-Induced Apoptosis

Tanaka¹,

Sasaki

Kamata³

et al. 2009

Molecular and Cellular Biology

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“…Since the role of Sam68 as signaling molecule has been recently reviewed (Najib et al 2005, Lukong & Richard 2007), herein, we will describe only the more recent observations related to human cancer.…”

Section: Role Of Sam68 In Signalingmentioning

confidence: 99%

The RNA-binding protein Sam68 is a multifunctional player in human cancer

Bielli

Busà

Paronetto

et al. 2011

Endocrine-Related Cancer

148

145

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Src associated in mitosis, of 68 kDa (Sam68) is a KH domain RNA-binding protein that belongs to the signal transduction and activation of RNA family. Although ubiquitously expressed, Sam68 plays very specialized roles in different cellular environments. In most cells, Sam68 resides in the nucleus and is involved in several steps of mRNA processing, from transcription, to alternative splicing, to nuclear export. In addition, Sam68 translocates to the cytoplasm upon cell stimulation, cell cycle transitions or viral infections, where it takes part to signaling complexes and associates with the mRNA translation machinery. Recent evidence has linked Sam68 function to the onset and progression of endocrine tumors, such as prostate and breast carcinomas. Notably, all the biochemical activities reported for Sam68 seem to be implicated in carcinogenesis. Herein, we review the recent advancement in the knowledge of Sam68 function and regulation and discuss it in the frame of its participation to neoplastic transformation and tumor progression.

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“…Sam68 is a member of the K homology domain-containing, RNA-binding, signal transduction-associated protein family, and has been suggested to be involved in various cellular processes, including RNA 3'-end formation, alternative splicing, cell cycle regulation, adipogenesis, neuronal development and tumorigenesis (5)(6)(7). Previously, Sam68 was identified to be frequently upregulated in cancer and has an oncogenic role in inflammatory carcinogenesis, tumor invasion and metastasis (8,9).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

Zhao

Tian

et al. 2015

Molecular Medicine Reports

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Abstract. Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism of NB remains to be elucidated. In the present study, reverse transcription quantitative polymerase chain reaction data demonstrated that the expression of Sam68 was significantly upregulated in NB tissues compared with their matched adjacent normal tissues. Furthermore, it was revealed that reduced expression of miR-203 and increased expression of Sam68 co-existed in NB tissues. Knockdown of Sam68 reduced the proliferation, migration and invasion of human SK-N-SH and SH-SY5Y NB cells. Similarly, overexpression of miR-203 also inhibited the proliferation, migration and invasion of these two cell lines. It was further demonstrated that the protein expression level of Sam68 was negatively mediated by miR-203 in the SK-N-SH and SH-SY5Y NB cells. Additionally, data from a dual luciferase reporter assay confirmed that miR-203 directly targeted Sam68 by binding to its 3'-untranslated region. In conclusion, the present study suggested for the first time, to the best of our knowledge, that the aberrant downregulation of miR-203 may contribute to the aberrant upregulation of Sam68 in NB and that miR-203 has an inhibitory role in malignant progression of NB by targeting Sam68. The present study provided evidence to support miR-203/Sam68 as a novel diagnostic or therapeutic targets for NB.

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Role of Sam68 as an adaptor protein in signal transduction

Cited by 57 publications

References 93 publications

A Novel RNA-Binding Protein, Ossa/C9orf10, Regulates Activity of Src Kinases To Protect Cells from Oxidative Stress-Induced Apoptosis

A Novel RNA-Binding Protein, Ossa/C9orf10, Regulates Activity of Src Kinases To Protect Cells from Oxidative Stress-Induced Apoptosis

The RNA-binding protein Sam68 is a multifunctional player in human cancer

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

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